Gellan gum tablet coating

ABSTRACT

A pharmaceutical composition comprising a tablet having a dried coating thereon, wherein the composition has a total weight of about 100 mg to about 1.5 g, the dried coating comprises about 0.025% to about 10% by weight of the total composition, and gellan gum is the principal component of the dried coating

CROSS REFERENCE TO RELATED APPLICATION

This is a continuation application of U.S. application Ser. No.09/308,043, filed Sep. 24, 2999, now U.S. Pat. No. 6,395,298, which isbased on PCT/US98/23430, filed Oct. 30, 1998, which claims the benefitof U.S. Provisional Application No. 60/064,454, filed Oct. 31, 1997,entitled “Gellan Gum Tablet Coating”, all of which are herebyincorporated by reference in its entirety.

FIELD OF THE INVENTION

This invention relates generally to tablet coatings and to a method toprepare compositions useful to coat tablets. More particularly thisinvention relates to a tablet coated with gellan gum, use of gellan gumas a coating, a method to prepare a gellan gum composition useful tocoat tablets, a gellan gum composition useful to coat tablet(s), and toa method for coating tablet(s) with gellan gum.

BACKGROUND OF THE INVENTION

Tablets are typically used to deliver a pharmacologically effectiveamount of a therapeutic drug to humans and animals so as to providemedicinal benefit to the human or animal. Typically such therapeuticallyeffective drugs include those drugs that possess and produce desirabledrug effects after effective consumption by the human or animal.

In medicinal uses, one or more coatings is desired on a medicinal tabletin order to obtain one or more of gloss, better appearance,identification, mouthfeel, stability, color, swallowability, improvedtaste and the like.

Many medicinal tablet coatings today are low viscosityhydroxypropylmethylcellulose (HPMC). Usually a HPMC solution of about10% weight with a viscosity below 1000 cps. (centipoise), withappropriate plasticizer, is applied by a spraying system or device to atablet in a coating process.

Even with the foregoing and other tablet coating compositions, theindustry continues to desire a product which provides enhanced tabletcoating properties. The industry has recognized the need for an improvedtablet coating which would provide increased gloss, better mouthfeel atcoating quantities at lower levels than conventionally accepted methods,for example. The process of preparing such an improved tablet coatingeconomically and efficiently continues to be of interest.

OBJECTS OF THE INVENTION

It is an objective of this invention to provide a tablet coatingcomprising gellan gum.

It is another objective of this invention to provide a tablet coatedwith gellan gum.

It is an additional objective of this invention to provide a process forpreparing a gellan gum composition useful for coating tablets.

It is yet another objective of this invention to provide a process forpreparing a coated tablet such as a coated placebo or a coatedpharmaceutical tablet comprising an active drug.

It is yet still an additional objective of this invention to provide atablet having one or more enhanced properties such as higher gloss,better mouthfeel, non-tackiness, being swallowable with little or noaccompanying liquid, better taste and the like.

The above objectives and other objectives are met in this inventionwhich is more particularly described hereinafter without limitation.

BRIEF SUMMARY OF THE INVENTION

In one embodiment, this invention comprises a tablet coating comprisinggellan gum. In another embodiment, this invention further comprises aplacebo or an active drug or pharmaceutical wherein the placebo or drugis coated with gellan gum. In another embodiment this invention furthercomprises a process for preparing a gellan gum composition useful forcoating a placebo or a coated pharmaceutical tablet which comprises thesteps of admixing gellan gum and water under effective shear conditionsto prepare an aqueous gellan gum coating composition thereof. In anotherembodiment this invention further comprises preparing the aforementionedaqueous gellan gum coating composition and applying the same in anadherent fashion to a placebo or a tablet containing a pharmaceuticalwhereby a gellan gum coated placebo or gellan gum coated pharmaceuticaltablet is formed and thereafter drying the same. In yet anotherembodiment of this invention, this invention comprises a method oftreating a patient in need of treatment which comprises administering tothe patient a therapeutically effective amount of a coated tablet,wherein said coated tablet comprises a tablet coated with gellan gum andwhich contains a therapeutically effective amount of a therapeuticallyeffective drug beneficial to said patient. Other embodiments of thisinvention are included herein and are described in more detailhereinafter.

DETAILED DESCRIPTION OF THE INVENTION

Gellan gum useful herein is that produced by inoculating a carefullyformulated fermentation medium with the microorganism Sphingamonaselodea (ATTC 31461). Gellan Gum is available from Monsanto Company, 800North Lindbergh Boulevard, St. Louis, Mo. 63167, USA. Typical brandnames include KELCOGEL® and GELRITE®. Gellan gum useful herein includesany form available form such as but not limited to, non-clarified,clarified, and partially-clarified native, deacetylated and partiallydeacetylated forms as well as mixtures thereof and the like. Kelcogel®and Gelrite® are registered trademarks of Monsanto Company. Gellan gummay be prepared according to the methods disclosed in U.S. Pat. Nos.4,326,052 and 4,385,123 both of which are incorporated herein theirentirety by reference.

Optional components of the gellan gum aqueous coating composition ofthis invention may include but are not limited to a color additive(s)and/or other coating polymers as will be readily apparent to those ofskill in the art in particular after reading this specification. Atypical plasticizer is glycerine although any equivalent orsubstantially equivalent plasticizer may be satisfactorily employedherein if desired.

The scope and utility of the present invention is not limited to anyactive ingredient. Active ingredients which may be effectively coatedusing this invention are not limited and include illustrativelypharmaceutical active ingredients and over-the-counter drugs (includingvitamins and nutritional supplements and the like) such as thosetypically delivered in a tablet dosage form. Examples include but arenot limited to analgesics and antiphlogistics such as aspirin,acetaminophen, phenacetin; steroids including antinflammatory steroids;enzymes, proteins, antibiotics or antimycrophotics including penicillinand its derivatives; anesthetics, vasodiolators such as nitroglycerin,anticarcinogins, sulfonamide drugs, sedatives, tranquilizing andhypnotic agents, bronchial-dilating agents, potassium chloride, mixturesthereof and the like.

The process for preparing a coated placebo or a coated (pharmaceutical)tablet comprising an active drug herein comprises the steps of admixinggellan gum and water under effective shear, heat and ionic conditions toprepare an aqueous gellan gum coating composition and applying theaqueous gellan gum coating composition in an effective fashion to aplacebo or to a tablet such as one comprising a pharmaceutical whereby agellan coated placebo or coated pharmaceutical tablet is formed. Adrying step typically occurs and typically follows.

The aqueous gellan gum coating composition useful to coat tablets ispreferably admixed in any suitable container or the like prior toapplying the gellan gum composition to or on a tablet to be coated.Initially the gellan gum and water are admixed and further mixing iscarried out under effective shear to form an aqueous tablet coatingcomposition. Typically the gellan gum coating aqueous composition priorto application of such effective shear will have a viscosity in therange from about 44 cps. to about 55,500 cps. and preferably from about2200 to about 50,000 cps although gellan gum compositions having greaterand lesser viscosities may sometimes be employed depending on a numberof factors.

If desired, gellan gum compositions comprising gellan gum and/or gellangum and one or more of a another ingredient such as a polymer such as,but not limited to, those selected from the group consisting ofhydroxypropyl celleulose, hydroxypropyl methyl cellulose, sodiumcarboxymethyl cellulose, sugar, aspartame, maltodextrin, tapiocadextrin, modified food starches, polyvinylpyrolidone, mixtures thereofand the like may be employed in this invention. As employed herein, theterm “gellan gum” includes gellan gum and/or compositions of gellan gumwith one or more of these polymers or a sugar.

The aqueous gellan gum composition of this invention may be mixed in orby any suitable mixing system preferably until substantially completemixing has been accomplished. Some heating may be necessary to achievedispersion and hydration of gellan gum. The amount of shear preferablyemployed is an effective amount, i.e., which produces a well mixedhomogenous gellan gum composition. The aforementioned admixing can becarried out by any convenient means including but not limited to use ofa propeller or stirrer system although generally stirring by aconvenient mechanical means is acceptable. Other forms of mixing can beemployed.

Optionally, if desired, various other ingredients may be employed in thegellan gum aqueous composition include any ingredient which iscompatible or can be made compatible with an aqueous gellan gumcomposition useful to coat tablets of this invention, (such as, but notlimited to, colors, color system(s), flavor(s), sweetener(s), mint(s),fragrance(s), plasticizer(s), active ingredient(s) and mixtures thereofand the like).

The gellan gum aqueous composition is preferably applied to thetablet(s) to be coated in a batch, semi-continuous or continuous processor some combination thereof in a manner which produces a satisfactorilyuniformly coated tablet. The gellan gum composition may be applied totablets to be coated using any satisfactory application and dryingsystem or combination of some application system and some drying system.The combination is not critical nor is the arrangement of equipment.

The amount of gellan gum in the gellan gum aqueous composition usefulfor coating tablets is about 0.1% to about 10% and preferably from about0.25% to about 5% by weight gellan gum of the total gellan gum aqueouscomposition although greater and lesser amounts of gellan gum may beemployed if desired. A most preferred range is about 0.075% to about 3%.

During application of the gellan gum aqueous composition to the tabletto be coated, the temperature of the gellan gum aqueous composition ispreferably in the range from about 25° C. to about 45° C. althoughgreater or lesser temperatures may be employed if desired. It ispreferred that the gellan gum composition be maintained in a solution ordispersion or an applicable state during its coating application to thetablet(s) to carry out this invention.

Historically those of skill in the art have considered a compositionhaving a viscosity of about 1,000 centipoise (cps) as being at the upperbound as regards usefulness as a coating composition due to that highviscosity. Since an aqueous composition comprising gellan gum (1.8% byweight gellan gum) and water has a viscosity of about 28,460 cps at atemperature of about 30° C., those of skill in the art would not haveconsidered such a composition useful to coat tablets and would have beensteered away from it for this invention. Now, however, the inventorshave surprisingly discovered that despite the high viscosity of a gellangum composition at room temperature that such compositions are veryuseful to coat tablets as the invention herein provides.

Gellan gum may be coated onto tablets which are uncoated or are thosetablets which have been coated with one or more prior coatings(overcoating) of an acceptable coating composition which allowsadherency with gellan gum. An initial coating may comprise one or morepolymers such as cellulosics, dextrins, acrylics, any colors or otherpharmaceutical coating material. A gellan gum composition may beemployed as a primary coating on a tablet, as a secondary coating on atablet, or as a tertiary coating if desired. One or more coatingapplications of gellan gum may be made to a coated or uncoated tablet inaccordance with this invention, although typically one coating iseffective and is preferred. If desired, a gellan gum coating may beapplied to a tablet in accordance with the invention in an instancewherein a protective coating is desired, for example to protect coatedor uncoated tablet from physical damage.

Typically the amount of gellan gum which is coated onto tablets inpracticing this invention is that amount which provides a gellan gumcoated tablet having a weight gain (during coating) from about 0.025% toabout 10% weight percent of the total tablet weight and preferably fromabout 0.05% to about 5% weight percent of the total tablet weightalthough larger and smaller weight percents may be employed if desired.Typically this amount of gellan gum is that amount which is necessary toprovide an effective or desired coating.

Neither the tablet shape nor the tablet size are critical. Preferredshapes and sizes are those which can be effectively consumed by a humanor animal recipient with relative ease. Preferable sizes of tabletsinclude but is not limited to those tablets which are about ¼ inch toabout ¾ inch in size and weigh from about 100 to about 1.5 grams eachalthough tablets may be employed which are larger or smaller in size andof lighter and heavier weight if desired. Preferred shapes are round oroval; however other shapes may be employed if desired.

Preferred tablets are medicinal tablets for humans or animals. Thetablets include but are not limited to tablets of any convenientcomposition which may or may not contain any pharmaceutically effectivedrug vitamin or nutrient or drugs suitable for human and/or animalconsumption. A gellan gum coating may be employed on tablets which areplacebos or blanks. Tablets useful herein include but are not limited totablets which are uncoated or have been coated one or more times. In oneembodiment a gellan gum coating may be the only coating and may comprisea first coating or a second or a third coating.

Illustrative colors and colorants useful herein include withoutlimitation, pigments, dyes, lakes and oxides (including titaniumdioxide) and the like, may be optionally employed with gellan gum usedin practicing this invention. The gellan gum aqueous composition mayoptionally contain a suitable color or colorants for application to acolored or noncolored coated or uncoated tablet.

Tablets to be coated according to this invention may be colored, neutralor have their natural color or may be absent color. If one of morecolors, dyes lakes, or pigments or mixtures thereof are employed in agellan gum coating composition herein, such as for example, an FDAcertified color, dye, lake, or pigment, the color or combination ofcolors is not critical and may be selected by those of skill in the artbased upon a need at the time of the coating operation. Examples ofsuitable pigments which are useful in this invention include, withoutlimitation, FD&C and D&C lakes, titanium dioxide, magnesium carbonate,talc, pyrogenic silica, iron oxides, channel black, insoluble dyes andmixtures thereof and the like. Also, nature pigments such as riboflavin,carmine 40, curcumin, annatto, mixtures thereof and the like areacceptable herein. Other examples of pigments suitable herein include,without limitation, these disclosed in Jeffries U.S. Pat. No. 3,149,040and Butler et al., U.S. Pat. No. 3,297,535, as well as in Colorcon U.S.Pat. No. 3,981,984. These three patents are incorporated herein byreference in their entirety. In the absence of a colorant, the gellangum composition typically produces a clear or substantially clearcoating on a coated tablet.

As employed herein, the term “tablet” includes without limitation,tablet, particle, micronized particle, particulate, pellet, pill, core,powder, granule, granulate, small mass, seed, specks, spheres, crystals,beads, agglomerates, mixtures thereof and the like. Typically thepreferred tablet will be in a form sufficiently stable physically andchemically to be effectively coated in a system which involves somemovement of the tablet, as for example in a fluidized bed, such as in afluidized bed dryer or a side vented coating pan, combinations thereofand the like. Virtually any tablet, placebo, the latter typicallylactose or sugar or mixtures thereof and the like, is acceptable hereinas a tablet to be coated in the practice of this invention.

Tablets coated according to this invention have a high gloss. Typicallythe gloss is in the range from about 200 to about 400 and preferablyfrom about 250 to about 350 although greater or lesser gloss may beemployed if desired. As referred to above, gloss is measured orcharacterized typically by use of a Tricor Systems, Inc., Model 805A,Surface Analysis System. Tablets of this invention typically have one ormore enhanced properties such as higher gloss, better mouthfeel,non-tackiness, being swallowable with little or no accompanying liquid,better taste and the like.

The gloss resulting from gellan gum coating of this invention issuperior in shine to conventional film coatings presently used in theindustry. Measurements of gloss on polymer coated tablets and commercialproducts were well below the gloss imparted with gellan gum prepared inaccordance with this invention as measured at TRICOR Systems. Gellan gumcoatings of this invention impart this gloss at weight gain levels thatare considerably lower than existing and accepted alternatives. As aresult of this high gloss from comparatively lower weight gains broughtabout by this invention, gellan gum is an attractive alternative toexisting aqueous form coatings.

This characteristic high gloss from low weight gains also makes gellangum an attractive alternative to sugar coating processing currently usedin the industry. Sugar coating processes currently use multiplematerials, extended processing times and multiple material handlingsteps. Superior gloss can be achieved with gellan gum at a fraction ofthe weight gain now required in sugar coating. This lower materialrequirements results in glossy tablets that can be manufactured muchfaster than current products and can also be formulated to produce asmaller, easier to swallow dosage.

As employed herein, the term “adherent” means that the gellan gumcoating effectively adheres to the coated tablet until consumption by apatient or animal to enable effective release of the active ingredienttherefrom so that the active is effectively made available to thepatient's biological systems to provide therapeutic value.

Although the gellan gum coating composition of this invention willinitially be an aqueous composition, the tablet coating will preferablybe dried or substantially dried prior to, upon its exit or removal fromthe coating application system or at sometime in preparing coatedtablets. The coated tablets may be placed in suitable packaging then ifdesired.

The amount of coating provided to the surface of the tablet is aneffective amount and is typically that amount which provides a minimumeffective coverage of the exterior surface area of the tablet, althoughthis invention also encompasses those instances where there is partialcoverage of the exterior surface as well.

If desired, one or more layers of gellan gum coating may be employedusing this invention. Those of skill in the art will be able todetermine the extent of any layering depending on the drug, tablet size,and its physical and chemical and therapeutic properties andcharacteristics from a reading of this specification and using theirskill in the art.

It is preferred that coating be continuous or nearly continuous and overthe surface of the tablet. An effective depth of coating is provided forretention. It is also desired that the tablet coatings herein besomewhat resilient with respect to handling, to peeling and to flakingand being rubbed off the coated tablet.

As referred to above, application of the gellan gum aqueous compositionas a coating to the tablet is preferably carried out by placing a tabletcapable of receiving and adhering a gellan gum tablet coatingcomposition of this invention in any acceptable coating applicationsystem. An acceptable coating application system is illustratively anysystem which has the capability to apply a gellan gum coatingcomposition of this invention to a tablet to provide an effectively,preferably uniformly coated tablet. For example, an acceptable coatingapplication system includes without limitation, a plain fluid bed system(i.e., one without any “Wurster” type insert), including a fluid bedspray tower of any reasonable size and design and systems similarthereto in function and utility.

Air Suspension Coating systems useful here as an illustrativeapplication system include those described in Ullman's Encyclopedia ofIndustrial Chemicals, Volume A16 pages 583-584 (1990) which includes adescription of the Wurster process. Ullman's Encyclopedia of IndustrialChemicals, Volume A16 pages 583-584 (1990-1996) is incorporated hereinby reference in its entirety. This incorporation includes the chapterMicroencapsulation authored by Christopher A. Finch of PentafinAssociates, Weston Turville, AYLESBURY HP 22 5TT, UK.

Also, acceptable for use to prepare coated tablets of this invention areillustratively a variety of side vented coating pans, spray dryer(s),continuous coating pans, and conventional coating pans, such as thosewith systems for mechanically providing the gellan gum composition to atablet in an effective manner using mechanical means as for example byspray nozzles or the like. Also acceptable as a spray tower system is aconventional fluid bed tower equipped with a suitable spray apparatus.Any application system capable of applying a composition of thisinvention to a tablet is an acceptable system for coating tabletsemploying the aqueous gellan gum coating composition of this invention.As the coating system is not critical, any size coating system isacceptable. Batch and continuous processes, semi-continuous and suitablevariations thereof are envisioned without limitation.

The “Wurster” type fluid bed dryer typically comprises a cylindricalouter vessel having a perforated floor through which a heated gas passesupwardly to heat and fluidize a batch of tablets or particles fed to orformal therein. A concentric, open ended inner cylinder is suspendedabove the center of the perforated floor of the outer vessel. A spraynozzle, or projecting part, centered beneath the inner cylinder sprays asolution of the coating material upwardly into the inner cylinder as thefluidized materials pass upwardly through the spray in the innercylinder. The particles circulate upwardly though the center of theinner cylinder and downwardly between the inner and outer cylinder. Theair that fluidizes the particles also serves to vaporize the watercausing the composition to deposit as a film or coating onto the surfaceof each particle. After repeated passes through the coating zone in theinner cylinder, a sufficient thickness of polymer accumulates over theentire surface of each particle as to coat each particle. A descriptionof an acceptable “Wurster” type fluid bed dryer is found in J. Am Phar.Assoc, Sci. Ed. Vol 48, (1959) Air Suspension Technique of Coating DrugParticles by Wurster, Dale E. and Preparation of Compressed TabletGranulations by the Air Suspension Technique II, Wurster, Dale E, Sci EdVol 49 (1960) both of which are incorporated herein in their entirety byreference. In operation of the dryer, the operator will typically havethe tablets discharged when the desired amount of coating has beenapplied to the tablets. This is generally based on the amount of coatingcomposition sprayed in the dryer from which based on prior experience,the amount of weight gain (%) of the tablets during coating can bedetermined. Electronic or equivalent controls are typically installed onthe dryer to regulate the process such as regulating the temperature ofthe inlet air and the amount of such inlet air and its pressure.

In side vented coating pan systems, as the material inside is coated itincreases in size and weight. Generally the materials to be coatedaccumulate adjacent an end wall and along a side wall of the drum in thesystem. As the drum rotates, the material is tumbled and is coated witha coating composition from one or more spray nozzles. Initially thematerial may form a mass and as the material is sprayed and increased insize the large particles migrate away from the end wall and cannotpenetrate the mass of smaller particle adjacent the end wall.Eventually, substantially all of the material is uniformly coated a suchthat the material forms a new mass wherein the particles are slightlylarger than the original mass formed by the uncoated particles. Theprocess repeats itself such that the particles are coated withadditional composition from the spray nozzle, thereby again increasingin size and weight and migrating away form the end wall. The cyclecontinues until the particle achieve a desired uniform size.

Particularly usefull self contained side vented coating pan system inthis invention are available under the Accela Cota brand sold by ThomasEngineering Incorporated, 575 West Central Road, Hoffman Estates, Ill.60195-0198, U.S.A. Various size pans may be satisfactorily employedherein and include without limitation 15, 24, 48 and 60 inch pans, ifdesired. The size of the pan and dryer are not critical. The Compu Labmodel sold under the Accela Cota brand works well for laboratory sizecharge (feed) quantities. Those of skill in the art will recognize thatvarious size pans may be employed depending on the amount of materialsto be coated and other coating operations.

The Accela Cota brand side vented coating pan system comprises arotating drum and as the drum is rotated containing the tablets to becoated, the coating composition is applied to the tablets by means ofone or more nozzles positioned within the rotating drum so as to directthe coating composition to the tablets in the bed. As the pan is rotatedand the coating composition is further applied to the tablets, thetablets achieve a desired coating. This apparatus is also a dryer forsubstantially drying the tablets as the tablets are coated. The sidewall of the drum is perforated and a flow of air is provided into thedrum through apertures for drying the coating composition on thetablets. A system is also provided on the apparatus for removing theoutlet air and for removing the coated tablets.

The nozzles of this side vented coating system are preferably adjustableand may be positioned nearer to and closer to the bed of tablets to becoated depending on the conditions of use and the desired coatingcomposition quality and quantity, among other factors. Those of skill inthe art will recognize that the distance of the nozzle or nozzles fromthe bed is important and may be adjusted to provide optimum coatingcompositions. In operation such nozzle placement distances will be aneffective distance and will be selected from a plurality of availablepositions and will depend on the tablets being coated, the coatingcompositions, the degree of coating desired and other conditions of theparticular coating operation, among other factors.

Those of skill in the art will recognize that one or more nozzles may beemployed as desired to provide optimum coating. The number of nozzles isnot critical and may be varied as needed depending on the coatingoperation and other factors. The nozzle throat diameter is typicallyfrom about 0.028 inch to about 0.100 inch although, greater and smallerthroat diameters may be employed. A nozzle throat diameter of somewhereabout 0.040 inch is preferred although that size is not critical. Thenozzle(s) is preferably aimed perpendicularly or nearly perpendicular tothe bed although other direction(s) of aim may be employed if desired.Those of skill in the art will recognize that the pan may be rotated ata speed selected from a plurality of operating speeds. The pan may bestopped after the material has been coated and the matter removed.

In general, an effective nozzle distance for applying a coating to atablet using a side vented pan coating system is in the range from beingpositioned less than about a ¼ inch from the bed to about 15 inches andpreferably from about 8 to about 12 inches although greater of lessernozzle distances may be employed if desired depending on the weight oftablets charged into the pan and coating system composition and otherfactors.

If desired, the same or a similar coating application system can beemployed for both a first and a second or sequential coatingapplications or different coating application systems may be employedfor a first or second or more coating applications. If desired, the samecoating application system can be used to apply a first and second ormore coatings with or without removal of the tablets from such a systembetween the first and second or more coatings.

While illustrative useful application systems have been describedherein, those of skill in the art will recognize that such descriptionis provided to provide information as to the possible application anduse herein in accordance with this invention. Those of skill in the artwill recognize that the actual operation of any such application systemwill vary and may be varied from “text book” type description of suchoperation in according with the parameters and conditions of any desiredoperation, among other factors. Configurational and design changes maybe made on such applications systems and operating parameters may bevaried.

The gellan gum coated tablets of this invention may be internallyconsumed by humans and animals in a typical customary manner.

EXAMPLES

Examples 1-18, are provided to illustrate the preparation of acceptablecoated tablets in accordance with this invention and are provided by wayof illustration and are not intended to limit the invention in any way.All percents and any parts are by weight unless otherwise indicated.These Examples illustrates the practice of this invention in a nonlimiting fashion. Various application systems including fluidized feedsystems and pan vented coated systems are illustrated withoutlimitation.

Example 1

An acceptable high gloss gellan gum coated (red colored) tablet wasprepared in this Example in accordance with this invention.

A gellan gum composition useful for coating tablets was preparedcomprising 30 grams gellan gum, 1968 grams water and two grams sodiumcitrate to provide a 1.5% by weight gellan gum aqueous compositionuseful for coating tablets.

This aqueous gellan gum composition was prepared by weighing the waterinto a clean dry residue free beaker and weighing out the gellan gum(Kelcogel) and sodium citrate. The water was then mixed with alaboratory mixer to create a vortex. The gellan gum powder and sodiumcitrate was slowly introduced into the vortex to achieve dispersion.Stirring was continued without heat to finalize the dispersion of gellangum. Heat was applied while stirring until the dispersion temperaturewas about 70° C. to hydrate the gellan gum. Care was taken to avoidcharring the resulting dispersion, i.e. employing sufficient stirringand avoiding overheating. The beaker was removed from the stir plate andcooled to ambient temperature to make the gellan gum aqueous compositionavailable for coating.

The tablets to be coated herein were uncoated placebos (½ inch, standardconcave shape, 390 mg. weight each).

A hydroxypropylmethylcellulose (HPMC) and color composition having theingredients shown in Table 1 below was applied to these uncoatedplacebos to prepare a tablet which had color and appearance mimickingrecognized commercial products using a Compu Lab side vented 15 inchcoating pan system as an application system.

TABLE 1 Ingredients: Weight (g) Pharmacoat 606 (10%) 1800 D-447 90 TA 30Water 130 Total Weight 2050 grams Red (D447) (Dye Dispersion) 11.83%Titanium Dioxide 23.64 grams 20.01% FD&C Red No. 40, Hi Dye Lake 40grams 8.18% FD&C Yellow No. 6 dye 16.36 grams 2.0% EDTA solution (40%) 4grams 57.98% Distilled Water 115.91 grams 199.91 grams Pharmacoat 606(10%) = hydroxypropyl methyl cellulose TA = triacetin (plasticizer)

The side vented pan coating system used herein employed one nozzle whichwas aimed more or less directly at the bed of tablets to be coated andwas positioned at a acceptable standard distance from the outer portionof that bed. That nozzle had a throat diameter of about 0.040 inch.Operating data was:

TABLE 2 Side Vented Coating Pan Operating Data, 1.9 Kg. Charged CoatingElapsed Composition Pan Air Time Wt (g) Temperature, ° F. PAN FlowAtomizing (Min) Sprayed Inlet Outlet RPM (CFM) Air (PSI)  0  0 72.0 49.010.2 238 45.2  4:10  38 69.5 48.5 10.2 238 44.6 10 117 68.5 49.4 10.2238 44.3 15 190 64.2 48.8 10.3 238 44.4 20 261 65.1 49.0 10.3 238 44.125 233 60.8 47.7 10.3 238 44.2 30 406 62.1 47.8 10.3 238 44.0 34:05 46661.9 47.8 10.3 238 44.1

These placebos (red colored) were then coated with the gellan gumaqueous composition (prepared in a first step of this Example) in thesame 15 inch diameter pan Compu Lab side vented coating system as anapplication system, the data of which is shown in the following Table 3.

TABLE 3 Side Vented Coating Pan Operating Data Charge = 1.9 Kg. pluscolor coating Elapsed Solution Pan Air Time Wt (g) Temperature, ° F. PANFlow Atomizing (Min) Sprayed Inlet Outlet RPM (CFM) Air (PSI)  0  0 64.546.6 24.3 200 25.9  4  73 61.2 41.5 24.3 220 25.4  8 126 66.3 42.7 24.3220 25.5 12 178 64.8 44.5 24.3 220 25.3 16 225 65.1 47.8 24.3 220 25.220 271 62.3 48.0 24.3 220 25.4 24 318 63.1 48.4 24.3 220 25.2 28 36561.0 48.3 24.3 220 25.1 32 407 59.0 47.3 24.3 220 25.6 36 453 60.3 47.524.3 220 25.5 40 499 60.0 47.5 24.3 220 25.1 44 544 59.9 47.6 24.3 22025.5 48 589 60.1 47.6 25.0 220 25.3 52 634 60.0 47.7 25.0 220 25.1 56678 59.9 47.8 25.0 220 25.5 60:30 730 60.0 47.7 25.0 220 25.3 64:30 77560.6 48.0 25.0 220 25.0 67:20 807 59.9 48.3 25.0 220 25.0

This application system employed one nozzle positioned in closeproximity to the tablet bed and aimed at the bed of tablets to becoated. This produced an acceptable high gloss gellan gum coatedplacebo.

Samples were taken after weight gains of 0.05, 0.1, 0.2, 0.3, 0.4, 0.5,0.6 and 0.7% respectively to document and monitor coating appearance andcharacter. Further, this Example provided acceptable tablets with veryhigh gloss and lubricious mouthfeel. This Example demonstrates the glossand mouthfeel attributes of the gellan gum coating of this invention andalso demonstrates the compatibiltiy of clear gellan gum coating with abase coating of polymer and lake color system. Tablets of this Examplehad a gloss equal to or better than the gloss of commercially availablesugar coated products.

Example 2

In a first step, an acceptable gellan gum aqueous coating compositionwas prepared according to Example 1.

The tablets to be coated herein comprised uncoated placebos (⅜ inch,rounded shape, 355 mg. weigh each, standard concave shape). Theseuncoated placebos were first coated with a polymer/color compositioncomprising:

TABLE 4 Ingredients: Weight (g) 606 (10%) 2000 SS-1092 125 TA 33 Water200 Total Weight 2358 g Brown (SS-1092) (40% solids): 37.2% TitaniumDioxide 37.2 grams 2.65% FD&C Yellow No. 6 Low dye Lake 2.65 grams 0.15%Red Iron Oxide 0.15 grams 2.0% EDTA solution (40%) 2.00 grams 58.0%Distilled Water 58.00 grams 100.00 grams SS = Spectrablends, fromWarner-Jenkinson* *Warner-Jenkinson: 107 Wade Avenue, South Plainfield,New Jersey 07080

This coating operation was carried out in a Compu Lab 15 inch sidevented coating system in a manner similar to that employed for the colorcoating in Example 1, above.

These once coated placebos were then fed to a Compu Lab 15″ pan sidevented coating system wherein a gellan gum coated high gloss tablet wasprepared. One nozzle was employed which was positioned in closeproximity to the bed of tablets to be coated.

Operating data is provided in Table 5 below.

TABLE 5 Side Vented Coating Pan Operating Data Solution AtomizingElapsed Wt (g) Temperature, ° F. PAN Air Time (Min) Sprayed Inlet OutletRPM CFM PSI  0  0 68.1 49.2 24.2 255 20.1  5:15  88 68.6 48.3 24.2 25519.7 10:15 191 70.0 48.5 24.2 255 19.9 15 295 70.0 48.8 24.2 255 19.520:30 421 70.1 49.0 24.2 255 19.5 25 524 69.9 49.0 24.2 255 19.7 30 64370.4 49.3 24.2 255 19.9 35 762 70.2 49.8 24.2 255 19.2

Samples were taken after weight gains of 0.1, 0.2, 0.3, 0.4, 0.5 and0.6% respectively to monitor coating character. This Example providedacceptable tablets of this invention with high gloss and lubriciousmouthfeel. This Example demonstrates the compatibility of clear gellangum coatin with polymer/oxide color systems in the base coat.

Example 3

High gloss gellan gum coated tablets were prepared by preparing in afirst step a gellan gum composition as described in Example 1 abovewhich contained 1.5% Kelcogel and 0.15% aspartame.

The tablets to be coated herein comprised uncoated placebos which werecoated with a polymer/color composition comprising:

TABLE 6 Ingredients: Weight (g) 606 (10%) 600 D452 (40%) 24 PEG 460 12Water 42 Total Weight 678 Red (D452) (Dye Dispersion) 12.0% TitaniumDioxide 420 grams 20.0% FD&C Blue 1, Hi Dye Lake 700 grams 2.00% FD&CYellow No. 6 dye 70 grams 6.0% FD&C Red No. 40 dye 210 grams 2.5% EDTAsolution (40%) 87.5 grams 57.5% Distilled Water 2012.5 grams 3500 grams

The application was carried out in a Compu Lab side vented coating 15″pan, the data of which is shown in Step A below.

TABLE 7 Step A Side Vented Coating Pan Operating Data Solution AtomizingElapsed Wt (g) Temperature, ° F. PAN Air Time (Min) Sprayed Inlet OutletRPM CFM PSI  0  0 69.9 47.4 15.0 245 42.1  6  95 70.2 45.5 15.0 250 41.4 8 137 70.2 46.6 15.0 250 41.3 12 213 69.9 46.9 14.9 250 41.4 17:10 30567.3 46.5 15.0 235 39.9 18 323 67.6 46.3 14.9 235 39.7 20 362 68.0 46.614.8 235 39.6 24:10 493 15.1

The once coated placebo from Step A above was then coated with a gellangum aqueous composition in a Compu Lab side vented coating 15′ pan in aStep B

TABLE 8 Step B Solution Atomizing Elapsed Wt (g) Temperature, ° F. PANAir Time (Min) Sprayed Inlet Outlet RPM CFM PSI  0  0 75.5 50.6 24.4 25524.4  4  69 69.1 47.3 24.4 270 24.4  8 144 72.3 50.0 24.4 255 24.4 12237 67.2 49.7 24.4 270 24.3 16 321 72.6 49.1 24.4 260 24.1 20 413 72.149.8 24.4 260 24.4 24:30 519 72.1 49.6 24.4 260 23.4 28:30 612 72.1 50.424.4 255 23.8

A sweet tasting high gloss acceptable coating was produced.

Samples were taken after weight gains of 0.1, 0.2, 0.3, 0.4 and 0.5%respectively to monitor coating character. Acceptable tablets wereprepared in this Example which had high gloss and lubricious mouthfeel.This demonstrates the compatibility of clear gellan gum coating withpolymer/dye color systems in the base coat.

Example 4

An acceptable tablet coating composition comprising a gellan gumcomposition was first prepared according to Example 1.

The tablets to be coated herein comprised uncoated active drugingredient tablets of about 400 milligram (mg.) weight each, which werefirst coated with a polymer/color coating composition comprising:

TABLE 9 Ingredients: Weight (g) Pharmacoat 606 (10%) 100 D-947 4 TA 2Water 42 Total Weight 148 Pink (D947) (Dye Dispersion) 37.6% TitaniumDioxide 47 grams 2.4% D&C Red No. 27 dye 3 grams 1.6% EDTA solution(40%) 2 grams 58.4% Distilled Water 73 grams 125 grams TA = triacitin

A fluidized bed dryer system (“Wurster” type) was employed to carry outa first coating of these initially uncoated tablets. The fluidized bedsystem comprised a 4 inch circular plexiglass column having a perforatedbase plate with about 150 holes each about ⅛″ diameter therein andhaving positioned in this base plate, a liquid spray nozzle whichprotruded about ¼ inch in the interior of the column above the baseplate. The spray nozzle had a 0.035 inch diameter throat and wasconnected externally to a coating solution supply system. An air supplysystem was connected to the base plate and an air outlet filterpositioned atop the column provided for the air outlet. The air supplysystem had a temperature regulator system on it. In operation thetablets to be coated were charged to this fluid bed dryer, compressedair was forced into and through the base plate and color coatingcomposition was sprayed by the spray nozzle into the bed of tablets fromthe coating solution supply system.

TABLE 10 Elapsed Time Solution Wt (g) Outlet Compressor (Min) SprayedFeed Temp ° F. Blower PSI 0 11.3 2.2 120 5 32 4 65 2.2 120 5 36 8 20 2.2116 5.5 36

An acceptable high gloss tablet was then prepared by coating over thecolor coated tablets prepared immediately above in the same fluidizedbed dryer as described above by applying the previously made gellan gumcoating composition of this Example to the color coated tablets. In thiscoated active product tablet, the color coat was the first coating(primary, initial, or base) and gellan gum was the second coating orovercoating.

TABLE 11 Elapsed Solution Time Wt (g) Outlet Compressor (Min) SprayedFeed Temp ° F. Blower PSI  0  0 2.5 120 5 32  4  46 2.5 120 5 32 8:10 92 2.5 122 5 32 12 134 2.6 122 5 32 16 179 2.6 122 5 32

Tablets produced in this Example were acceptable and had high gloss andlubricious mouthfeel. These tablets were essentially the same as theacceptable tablets produced in the previous Example. In this Example, afluid bed system was employed as an application system whereas a sidevented coating pan was employed as an application system in the previousExample.

Example 5

An acceptable gellan gum coating composition was prepared according toExample 1.

The tablets to be coated herein comprised active ingredient tablets ofabout 476 mg weight each, which was first coated with a polymer/colorcoating composition comprising:

TABLE 12 Ingredient Weight 606 (10%) 100.0 D-452 (40%) 4.0 PEG 400 2.0Water 7.0 Total Weight 113.0 g Red (D452) (Dye Dispersion) 12.0%Titanium Dioxide 420 grams 20.0% FD&C Blue 1, Hi Dye Lake 700 grams2.00% FD&C Yellow No. 6 dye 70 grams 6.0% FD&C Red No. 40 dye 210 grams2.5% EDTA solution (40%) 87.5 grams 57.5% Distilled Water 2012.5 grams3500 grams

This first coating was carried out in a fluidized bed dryer as describedin Example 4.

TABLE 13 Elapsed Solution Time Wt (g) Temperature, ° F. Compressor (Min)Sprayed Feed Inlet Outlet Blower PSI 0  0 2.2 186 132 5 32 4 47 2.3 186127 5 32 8 87 2.3 186 127 5 32 10:30 108  2.3 187 129 5 32

In a second step of this Example 5, a high gloss gellan gum coatedtablet was prepared by coating the once coated tablet preparedimmediately above in a fluidized bed dryer as described above with agellan gum composition, the data of which follows in Table 14.

TABLE 14 Elapsed Solution Time Wt (g) Temperature, ° F. Compressor (Min)Sprayed Feed Inlet Outlet Blower PSI  5  53 2.35 179 127 5 32  9  89 2.4179 128 5 32 14 137 2.4 178 127 5 32 21:30 200 2.4 176 125 5 32

Tablets produced in this Example were acceptable and had high gloss andlubricious mouthfeel. These tablets were essentially the same as theacceptable tablets produced in the previous Example.

Example 6 Application of a Clear Gellan Gum Coating to an UncoatedTablet

Purpose: To apply clear coating of an aqueous gellan gum composition touncoated uncolored tablets to provide an acceptable high gloss coatedtablet of this invention.

Method: Using a 1.5% gellan gum solution useful for coating tablets

% Grams 1.5% Gellan Gum 22.5 grams 0.10% Sodium Citrate** 1.5 grams98.4% Deionized Water 1476.0 grams 1500 grams **Dihydrate, powder

Using a suitable mixing blade and mixer, with good vortex the gellan gumwas slowly added to water. Once the gellan gum was dispersed sodiumcitrate was added and heating initiated. Heat to 70° C. Allow solutionto cool and form gel.

Coating procedure: Spray 200 grams of 1.5% gellan solution (roomtemperature) onto 420 grams uncolored active ingredient tablets using alaboratory fluidized column (similar in concept to an Aeromatic Strea1). Samples of tablets were taken at 0.05, 0.1, 0.2, 0.3, 0.4 and 0.5%weight gains respectfully.

Application of 1.5% Gellan Gum to Uncoated Tablet

Weight Time Sprayed Inlet Exhaust Pump Compressor Min. Grams Temp (° F.)Temp (° F.) Setting PSI 0 5.5 162 127 2.5 32  4:30 58.5 168 119 2.5 30 8:30 100.0 173 123 2.5 32 13:00 146.5 173 123 2.5 32 16:00 177.5 175123 2.5 32 18:40 200 175 123 2.5 32

In this Example, acceptable tablets were produced which had very highgloss and lubricious mouthfeel. This Example demonstrates that gellangum coating of this invention can be successfully coated onto a tabletabsent a base coating on that tablet. The resulting gloss was judgedsuperior to commercially available clear coatings (non gellan gum) andcommercially available sugar coatings.

Example 7

Preparation and evaluation of the viscosity of 1.8% and 2.0% gellan gumcomposition to be measured for viscosity over a temperature range ofabout room temperature to about 60° C. and also to be coated onto colorcoated tablets.

These solutions of gellan gum were sprayed onto color coated tablets attemperatures between 24° C. and 30° C. (with viscosities ranging from+28,000 cps to 55,000 cps).

Materials: Gellan Gum Deionized Water Na Citrate Procedure: A 1.8%gellan and a 2% gellan solution were made as Example 1 1.8% Gellan Gum =1.8% = 27.9 g Deionized Water = 98.08% = 1471.2 g Na Citrate = 0.12% =1.8 g TOTAL 1500 g 2.0% Gellan Gum = 2.0% = 30.0 g Deionized Water =97.87% = 1468.05 g Na Citrate = 0.13% = 1.95 g TOTAL 1500 g

Viscosity Measurements

Spindle=3, Vessel=600 ml beaker, DV-I+Brookfield Viscometer, Viscositywas measured while solutions cooled.

1.8% by wt. 2.0% by wt. Gellan Gum Gellan Gum Temp. Viscosity Speed TempViscosity Speed ° C. (cp) RPM ° C. (cp) RPM — — — — — — 60 44 100 — — —50 60 100 48 89 100 40 127 100 40 164 100 35 2200 50 34.6 17680 5 *3028460 2.5 30 39740 2.5 **25 38730 2.5 *28 45600 2.0 — — — **24.6 554402.0 Key: *Viscosity measured before start of coating application totablets **Viscosity measured after coating application was completed totablets

1.8% Gellan gum

Brookfield Engineering Laboratories, Inc., 240 Cushing Street,Stoughton, Mass. 02072-2398

Application as a Coating to a Tablet Using a Fluid Bed Dryer

Time Weight Inlet Exhaust Pump Compressor Min. Sprayed Temp ° F. Temp °F. Setting PSI H/B 0 5.5 158 131 2.5 32 H8 4:00 54.0 103 121 2.5 30 B58:00 92.0 167 122 2.5 32 B5 12:30 137.5 168 122 2.5 31 B5 16:30 176.5167 123 2.5 32 B5 20:00 200 169 123 2.5 32 B5

The temperature of 1.8% Gellan at end of run was 26.0° C.

2% Gellan Gum

Application as a Coating to a Tablet Using a Fluid Bed Dryer

Time Weight Inlet Exhaust Pump Compressor Min. Sprayed Temp ° F. Temp °F. Setting PSI H/B 0 6.0 174 140 3.0 32 H8 1:00 22.0 170 128 3.0 32 4:0072.0 174 119 2.5 32 8:00 113.0 177 127 2.5 32 H8 14:00 180.0 176 127 2.532 B5.6 15:45 200 178 128 2.5 32

There was no problem spraying an aqueous gellan gum composition at 1.8%or 2.0% at room temperature at a viscosity ranges between about 28,460cps at about 55,500 cps using conventional peristaltic pumping andstandard nozzle apparatus.

Samples were taken after weight gains of 0.05, 0.1, 0.2, 0.3, 0.4 and0.5% respectively to monitor coating character. In this Example,acceptable tablets were produced having high gloss and lubriciousmouthfeel. This Example showed that gellan gum aqueous coatingcompositions can be successfully employed according to this invention at1.5%, 1.8% and 2.0% solids. Gloss and mouthfeel are not compromised whenapplying (via spraying) higher solids coating compositions.

Example 8

Preparation of a 1.8% by weight and 2.0% by weight aqueous gellansolution to be used for spraying a clear coating of gellan gum onto acolor coated tablet. The gellan gum solutions will be sprayed at anelevated temperature.

Materials: Gellan Gum Deionized Water Na Citrate Procedure: Solutionswere made: 1.8% Gellan Solution (1L) Prepared Gellan Gum = 1.8% = 18.0 gDeionized Water = 98.08% = 980.8 g Na Citrate = 0.12% = 1.2 g TOTAL 1000g 2.0% Gellan Solution (2L) Prepared Gellan Gum = 2.0% = 40 g DeionizedWater = 97.87% = 1957.4 g Na Citrate = 0.13% = 2.6 g TOTAL 2000 g

Prepared gellan solutions (1.8% concentration and 2.0% concentration)were then sprayed onto tablets using the fluid bed coating equipment.The solution were sprayed at 40° C. where viscosity of each solution isbelow 200 cps.

1.8% Gellan Gum Solution at 40° C.

Weight Inlet Exhaust Pump Compressor Time Sprayed Temp ° F. Temp ° F.Setting PSI 0 0 142 125 2.3 32 4:00 32 159 127 2.3 32 8:30 75.5 172 1252.3 32 12:00 109.5 169 126 2.3 32 18:25 166.6 164 125 2.3 32

2.0% Gellan Gum Solution at 40° C.

Weight Inlet Exhaust Pump Compressor Time Sprayed Temp ° F. Temp ° F.Setting PSI 0 0 150 127 2.3 32 8:00 75.5 168 127 2.3 32 14:00 174.5 166127 2.3 32 16:42 150 165 128 2.3 32

Heating the solution to lower viscosity had no detrimental effect on thecoating delivered to the tablets. Spraying at elevated temperaturesallows for high solids at lower viscosity and delivers a film comparableto lower solid solutions sprayed at room temperature.

Example 9

Gellan with pigment sprayed onto tablets. Pigment addition to gellancoating solutions at room temperature is difficult due to viscosity ofgellan solution. Pigment is easily dispersed, however, when gellancoating solution is heated to 40° C. or above. At this temperature thecoating solution is fluid (viscosity below 200 cps) and dispersion ofpigments in gellan solution is easily achieved with a standardlaboratory mixer.

Gellan solution: Follow procedure recited in Example 1.

Formula:

1.5% Gellan gum 45 grams 0.1% Sodium Citrate 3 grams 98.4% DeionizedWater 2952 grams Sodium Citrate (a sequestrant)

1000 grams of above gellan coating solution (1.5% gellan) is held at 40°C. To this preparation is added 3.0 grams Propylene Glycol and 3.0 gramsof Lecithin (Alcolec F-100) while mixing. The color component (7.5 gramsof Green—Spectra Spray SS-1091) is added but while mixing and holdingsolution temperature at 40° C. or above. Mix until homogenous.

Grams of gellan/color preparation from above was then sprayed onto 420grams of tablets in a fluidized bed coating apparatus. The 420 grams oftablets is a combination of 25 grams of tablets with active ingredientsand 395 grams of placebo tablets. Samples of tablets were taken at 0.5,1.0, 2.0, 2.5 and 3.0% weight gains respectively.

Tablets prepared in this Example had high gloss, uniform color andlubricious mouthfeel. This Example demonstrates the compatibility ofgellan gum with lake color system for aqueous film coating.

Example 10 Gellan Clear Coating Sprayed on Gellan/Color Coated TabletsFrom Example 9

Tablets from Example 10 which were coated with gellan and color coatingsolution (gellan, Green Spectra Spray, Propylene Glycol and Lecithin)were taken and coated again with a clear gellan coating solution alsosprayed at 40° C. (1.5% gellan). This demonstrates the compatibility ofgellan/color coating with gellan when used as a top coating or glosscoat. The top coating of clear gellan was applied at 40° C. with a totalweight gain of 0.5%. Samples were taken at 0.05%, 0.1%, 0.2%, 0.3%, 0.4%and 0.5% with gloss increasing with each additional weight gain of clearcoating.

Tablets prepared in this Example had a higher gloss than the tablets ofExample 10. These tablets also had a lubricious mouthfeel. This Exampledemonstrates the ability of this invention to improve tablet gloss whenusing clear gellan gum coating as an overcoat or as a gloss coating.This Example also demonstrates the compatibility of gellan gum coatingwith a base coat comprising gellan gum and lake color. Coated tabletsproduced herein have gloss and appearance which is better than orequivalent to commercially manufactured sugar coated tablets.

Example 11 Gellan Gum With Pigment (Oxides)

Using 1.5% gellan gum solution prepared in example 11, maintain gellansolution at 40° C. and add color/plasticizer system as in example 10.

Color system added to 1000 gram gellan solution:

3.0 grams Lecithin (Alcolec F-100)

3.0 grams propylene glycol

7.5 grams Oxide (Spectra Spray 1092)

Pigment disperses easily in gellan solution at 40° C because of lowviscosity of heated solution.

760.1 grams of gellan/oxide preparation were sprayed at 40° C. onto 420grams of tablets in a fluidized columns (similar to Aeromatic Strea 1).Samples were taken at 0.05%, 0.1%, 0.2%, 0.3%, 0.4% and 0.5% weightgains.

Tablets were produced in this Example that had high gloss, uniform colorand lubricious mouthfeel. This Example demonstrates the compatibility ofgellan gum with lake color systems and plasticizer in aqueous filmcoating systems.

Example 12 Gellan Gum Coating On Vitamin Tablets And Placebos

Purpose: To apply clear coating of Gellan gum solution to coloredvitamin tablets to demonstrate that acceptable gloss can be obtained.

Method: Using a 1.5% Gellan solution:

1500 grams total:

% Grams 1.5% Gellan Gum 22.5 grams 0.10% Sodium Citrate** 1.5 grams98.4% Deionized Water 1476 grams **Dihydrate, powder

Mixing Instructions: Follow procedure recited in Example 1.

Coating Instructions: Follow procedure recited in Example 4 (sprayed atroom temperature).

Tablets used totaled 420 grams (210 grams peach colored vitamins and 210grams of uncoated placebo tablets)

In this Example, acceptable tablets were also produced which result invitamin tablets and placebo tablets that had a high gloss and lubriciousmouthfeel. This Example demonstrates that gellan gum applied as a clearaqueous coating in accordance with this invention is compatible withvitamins and placebo tablets and results in tablets having an improvedgloss and mouthfeel over the uncoated tablets.

Example 13 Gellan Gum Coating On Vitamin Tablets And Placebos Sprayed At40° C.

Purpose: To apply clear coating of Gellan gum solution to coloredvitamin tablets to determine if appropriate gloss can be obtained.

Method: Using a 1.5% Gellan solution:

1500 grams total:

% Grams 1.5% Gellan Gum (Ex 8096*) 22.5 grams 0.10% Sodium Citrate** 1.5grams 98.4% Deionized Water 1470.0 grams **Dihydrate, powder

Mixing Instructions: Follow procedure recited in Example 1.

Coating Instructions: Follow procedure recited in Example 1 (sprayed at40° C).

Tablets used totaled 420 grams (210 grams peach colored vitamins and 210grams of uncoated placebo tablets)

In this Example, acceptable coated tablets were produced in accordancewith this invention which had high gloss and lubricious mouthfeelcomparable to the tablets from Example 13. This Example demonstratesthat ability of gellan gum to be processed in accordance with thisinvention at elevated temperatures with no negative impact on gloss ormouthfeel of the coated tablets.

Example 14

Gellan Gum With Pigment: Lake With PEG 400 Increased*

*Rather than 20% PEG 400 of total gellan gum solids, 50% PEG 400 ofgellan solids will be evaluated

Gellan solution preparation: Follow procedure recited in Example 1.

Mixing instructions: Follow procedure recited in Example 1.

Coating Preparation:

600 grams 1.5% Gellan solution (heated to 40° C.) 4.5 grams Peach(SS-1094) 4.5 grams PEG 400 Peach (SS-1094) (40% solids) 37.2% titaniumdioxide 37.2 grams 2.65% FD&C yellow no. 6 low dye lake 0.15% red ironoxide 0.15 grams 2.0% EDTA solution (40%) 2.00 grams 58.0% distilledwater 58.00 grams

Coating trial: (5-71-74-2) Spray 581.5 grams of above formula (40° C.)onto 420 grams placebos using a fluidized column (similar in concept toan Aeromatic Strea 1). Samples of tablets taken at 0.5, 1.0, 1.5, 2.05weight gains.

This resulted in improved and acceptable film flexibility, improvedgloss and good tablet coverage. This Example results in acceptabletablets with high gloss and lubricious mouthfeel. This Exampledemonstrates the compatibility of gellan gum with lake color systems andplasticizer at elevated concentrations. The elevated plasticizer levelenables greater film flexibility.

Example 15 Gellan Gum With Pigment: White Formula

*Gellan solution preparation: Used 1000 grams from solution made above,which had cooled to around 40° C.

Coating preparation:

1000 grams 1.5% gellan solution 9.4 grams White (SS-1031) (50% solids)3.0 grams Propylene Glycol 3.0 grams Lecithin (Alcolec F-100) White(SS-1031) (50%) solids 25% titanium dioxide 50 grams 25% talc 50 grams2.5% EDTA solution (40%) 5 grams 47.5% distilled water 95 grams

Weigh gellan solution into appropriate beaker (37.5° C.). Add PropyleneGlycol and lecithin. Stir, with an appropriate stirrer until it is mixedwell. Add white dispersion. Keep temperature around 40° C. prior tospraying. Combined at this temperature, pigment dispersed easily andmixed into the gellan solution with no problems.

Coating trial: Spray 711.2 grams of above formula (40° C.) 420 gramsplacebos* using a fluidized column (similar in concept to AeromaticStrea 1). Samples of tablets taken at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0%weight gains.

*25 grams active tablets part of charge

The Example produced acceptable tablets that had good lubriciousmouthfeel and gloss characteristics that are higher than commerciallyavailable white coating systems. This

Example demonstrates that gellan gum is compatible with titanium basedcolor systems and plasticizers. This Example also demonstrates gellangum's ability to impart gloss in the presence of these ingredients.

Example 16 Gellan Gum With Pigment: Lake (With HPMC Addition)

Using 1.5% gellan solution prepared above.

Coating preparation:

1000 grams 1.5% gellan solution

7.5 grams Green (SS-1091)

3.0 grams Hydroxypropylmethylcellose (Pharmacoat 606)

3.0 grams PEG 400

where PEG=polyethylene glycol 400 and Green (SS-1091) comprised:

38.4% titanium dioxide 76.8 grams 2.65% FD&C yellow No. 6 low dye lake2.65 grams 0.15% red iron oxide 0.15 grams  2.0% EDTA solution (40%)2.00 grams 58.0% distilled water 58.00 grams for a total f 200 grams

Weigh gellan solution into appropriate beaker and heat. Add PEG 400 andHPMC (temperature when added=60° C.). Mix with an appropriate stirreruntil dissolved. Add lake dispersion until it is mixed well.

Coating trial: Spray 760.1 grams of above formula (40° C.) 420 gramsplacebos* using a fluidized column (similar in concept to an AeromaticStrea 1). Samples of tablets taken at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0%weight gains.

*25 grams active tablets as part of charge (charge is the tablets to becoated which are provided to the fluidized column)

Results: Tablets coated to a 3% weight gain; addition of HPMC improvedfilm flexibility and enabled formulae to be made with PEG added at astandard level (20% of gellan solids level); gloss was not compromisedand is close to that which was obtained in tests using gellan withlecithin and PG. This Example further resulted in acceptable tabletswith a higher gloss than tablets coated with HPMC alone. Also, thetablets of this Example prepared in accordance with this invention, hadthe lubricious mouthfeel characteristic of gellan gum coatings. Further,this Example demonstrated the compatibiltiy of gellan gum with HPMC.

Example 17 Use of a Side Vented Coating Pan as a Successful ApplicationSystem

A

24″ pan Accela Cotta 16 Kg. charge color coated

1.5% gellan gum, pan RPM 13

Process air Vol. 440CFM

T=72° C. (Inlet)

Exhaust air temperature 50-52° C.

Two ¼ Jau Tips 40100 liq cap. (0.040 inch internal diameters, 0.100 inchexternal diameter from Spray Systems)

134255-45 Air cap.

Atomizing Pressure 24-25 PSI

Feed Rate 55-70 g/min

B

60″ Pan Acella Coata successful coating Charge 350 KG Process Color CoatGelan Gum Coat Air Volume 5500 cfm 5500 cfm Temperature 70° F. 75° F.(Inlet) Exhaust T 47 52 Spray Rate 1200 g/m 1200 g/min Solids 12% 1.5%Atomizing Air 40 psi 25 psi

The Example provided acceptable tablets with high gloss and lubriciousmouthfeel. This Example demonstrates the ability of gellan gum aqueousfilm coating system of this invention to be operated and scaled up frombench top equipment to a commercial size equipment.

Example 18 Gellan Gum Coating Solution with Dye Dispersion

A tablet coating composition comprised of a gellan gum composition wasfirst prepared (1.5% gellan concentration) according to Example 1.Tablets (420 grams) were coated using a fluidized column (similar inconcept to an Aeromatic Strea 1). These tablets were coated with apolymer/color coating composition and the gell gum solution which werecombined as follows:

1000 grams 1.5% gellan solution

3.75 grams Green dye dispersion (D412)

3.0 grams Propylene Glycol

3.0 grams Lecithin (Alcolec F-100)

Weigh the gellan into a beaker and add the propylene glycol and lecithinwhile gellan preparation in +40° C. Once the propylene glycol andlecithin are dispersed, add the dye dispersion.

807.8 grams of above formula were sprayed onto 420 grams of tablets (395grams of placebos and 25 grams of tablets with active drug substance).

Inlet Exhaust Heater/ Temp Temp Pump Comp Blower Run Time Weight ° F. °F. Setting Setting H B 57184-1 0 5.5 175 123 2.2 32 8:00 89.5 187 1262.3 32 9 5.3 15:00 181.5 190 124 2.5 32 23:00 287.0 190 123 2.5 32 30.00381.5 190 123 2.5 32 35:00 450.0 191 123 2.5 32 45:00 593.0 191 124 2.532 60:00 787.5 191 125 2.5 32 61:45 812.5 192 126 2.5 32

This Example provided acceptable tablets with very high gloss andlubricious mouthfeel. This Example further demonstrates thecompatibility of gellan gum with dye color systems and plasticizer.

Thus, it is apparent that there has been provided, in accordance withthe instant invention, a process that fully satisfies the objects andadvantages set forth herein above. While the invention has beendescribed with respect to various specific examples and embodimentsthereof, it is understood that the invention is not limited thereto andmany alternatives, modifications and variations will be apparent tothose skilled in the art in light of the foregoing description.Accordingly, it is intended to embrace all such alternatives,modifications and variations as fall within the spirit and broad scopeof the invention.

What is claimed is:
 1. A pharmaceutical composition comprising a tablethaving a dried coating thereon, wherein the composition has a totalweight of about 100 mg to about 1.5 g, the dried coating comprises about0.025% to about 10% by weight of the total composition, and gellan gumis the principal component of the dried coating.
 2. The composition ofclaim 1 wherein the dried coating further comprises at least oneadditive selected from the group consisting of a color, a plasticizer,and a surfactant.
 3. The composition of claim 1 wherein the driedcoating is a primary coating.
 4. The composition of claim 1 furthercomprising a second dried coating comprising a polymer other than gellangum.
 5. The composition of claim 4 wherein the second dried coating is aprimary coating.
 6. The composition of claim 1 wherein the dried coatingis the only coating.
 7. The composition of claim 1 wherein the level ofgloss of the dried coating is about 200 to about 400 when analyzed usinga surface system analyzer.
 8. The composition of claim 7 wherein thelevel of gloss is about 250 to about
 350. 9. The composition of claim 1wherein the tablet comprises an active drug.
 10. The composition ofclaim 9 wherein the dried coating comprises about 0.05% to about 5% byweight of the total tablet.
 11. The composition of claim 10 wherein thedried coating comprises about 0.075% to about 3% by weight of the totaltablet.